The objectives of this research are to define the series of distinctive cytological changes that cells in the inner nuclear layer of the retina undergo to become mature, functional cells. Differentiation of bipolar and horizontal cells and their synaptic contacts will be analyzed by the Golgi technique and conventional EM in normal mice and mice with either genetically or light induced photoreceptor degeneration. Two mouse mutant, pcd and rd, with different genetic lesions resulting in complete photoreceptor cell death but over very different time periods will be studied. The morphological response of cells in the inner nuclear layer under three very different conditions of removal of primary input will be analyzed. The inner layers of the retina will serve as a model for plasticity of neuronal elements in other areas of the CNS when the primary input is removed. In addition to differentiation, the involvement of glycoproteins and other polysaccharide containiing macromolecules in cell surface interactions during synapse formation will be studied in the retina to gain insight into the area of interneruonal recognition. Cell surface characteristics will be studied by using microbial carbohydrate-specific antibodies plus peroxidase or ferritin conjugated plant lectins. Glycoproteins will be localized during synapse formation by EM autoradiography after intravitreal injections of 3H-fucose. Specific EM stains for extracellular polysaccharide containing macromolecules will also be used to study cell surfaces during differentiation and synaptogenesis. Just as mutant bacterial strains have played a major role in our understanding of genetic mechaisms, mutant mice strains are facilitating our understanding of the mechansims of cellular differentiation in the CNS.